The Center for Gamma-Ray Imaging (CGRI) is an NIBIB-funded biotechnology-development resource whose scope includes the development of advanced gamma-ray detectors and imaging systems, the development and application of tools for the objective assessment of image quality and for system optimization, and the application of these imaging systems to important biological problems via internal and collaborative research and service to the biomedical community. This application is for a Competing Supplement, now called a Revision, for instrument upgrades to CGRI's flagship FastSPECT II imager in order to implement the new concept of adaptive imaging. In recent work, we have investigated the concept of adapting the imager configuration to optimize image quality for a particular imaging subject rather than a population of subjects. This involves acquiring and analyzing preliminary scout data and making automated decisions for setting the adjustable parameters in the system. We have completed a prototype single-camera adaptive SPECT system, we have developed a theoretical framework for the computations required to adapt a system optimally to a particular subject and task, and we have analyzed the benefits of creating feedback rules that involve data from a complementary modality such as X-ray computed tomography (CT). These preliminary studies have led us to the conclusion that adaptive SPECT represents a significant advance in molecular imaging that will have impact in both laboratory and clinical settings. Our specific request in this supplemental proposal is for capital upgrades that replace the 16 fixed modular gamma cameras in the FastSPECT II system with a full complement of updated and radially translatable cameras, and for the fabrication and motorization of a matching adjustable aperture assembly. The development of adaptive small-animal SPECT is a specific aim in the Center for Gamma-Ray Imaging's on-going funding, and increasing the scope of the project to include implementation on one of the Center's most utilized systems will provide opportunities for demonstrating the benefits of adaptive imaging in cancer, cardiac disease, and neuroimaging. [unreadable] [unreadable] [unreadable]